The overall goal of this work is to develop and apply a new MRI technique, fiber tracking, to the study of Alzheimer's disease (AD). It has been postulated that memory loss in AD is caused by functional isolation of the hippocampal formation due to neuronal loss, neurofibrillary tangle (NFT) formation, and the consequent disruption in neuronal connections. In the present study, we will develop a method for performing tract tracing in vitro in autopsy specimens, with the ultimate goal of adapting the method for in vivo clinical studies. Tract tracing will be performed by monitoring the directionality (anisotropy) of water diffusion in a magnetic resonance imaging (MRI modality (hereafter referred to as diffusion MRI. This method will provide formerly inaccessible information on the integrity of neuronal projections in human tissue. It is applicable to in vivo human studies due to its non-invasive nature and therefore provides a novel approach to diagnosing and following the progression of AD. This study is base on three hypotheses. First, anisotropy of water diffusion inside brains is due to the orientation of axons and/or their myelin sheaths: brain water diffuses preferentially parallel to fiber directions. Thus, by tracking the dominant path of water diffusion, neuronal fibers can be reconstructed. Second, degradation in fiber structures due to AD alters the properties of water diffusion and can be detected by the diffusion MRI technique. Finally, the study of fiber integrity by diffusion MRI can be performed on fixed brains, in which fiber structures (axons/myelin) should remain intact. Fixed tissues allow to perform time-demanding high resolution imaging without motion artifacts, which greatly enhances the efficiency of this study. In order to test these hypotheses, three dimensional (3D) fiber structures of brains will be reconstructed from 3D diffusion MRI measurements and the results will be validated by comparing the results with histology and with literature on fiber tracking studies (Aim 1). Fiber structure of human brain will be reconstructed using fixed human brains with and without AD. This study will provide information on extent and nature of fiber degradation due to AD (Aim 2). For the future use in clinical study, the technique for clinical in vivo 3D diffusion measurement will be developed (Aim 3). Due to the limited scanning time and significant motion artifacts in clinical study, the effort will be focused on development of rapid measurement and suppression of motion artifacts.